GENE MUTATIONS

aka point mutations

2016 Paul Billiet ODWS

Gene mutations affect only one gene

DNA sequence
Transcription
mRNA sequence
Translation
Polypeptide

2016 Paul Billiet ODWS

 Normal gene
DNA (antisense strand) GGTCTCCTCACGCCA

mRNA CCAGAGGAGUGCGGU
Codons

Polypeptide Pro-Glu-Glu-Cys-Gly
Amino acids

The antisense strand is the DNA strand which acts as the

template for mRNA transcription
2016 Paul Billiet ODWS
Mutations: Substitutions
Normal gene Substitution mutation
GGTCTCCTCACGCCA GGTCACCTCACGCCA

CCAGAGGAGUGCGGU CCAGUGGAGUGCGGU
Codons

Pro-Glu-Glu-Cys-Gly Pro-Val-Glu-Cys-Gly
Amino acids
Substitutions will only affect a single codon
Their effects may not be serious unless they affect an amino acid that
is essential for the structure and function of the finished protein
molecule (e.g. sickle cell anaemia) 2016 Paul Billiet ODWS
The genetic code is degenerate

A mutation may have no effect on the phenotype

Changes in the third base of a codon often have
no effect.

2016 Paul Billiet ODWS

No change
Normal gene Substitution mutation
GGTCTCCTCACGCCA GGTCTTCTCACGCCA

CCAGAGGAGUGCGGU CCAGAAGAGUGCGGU
Codons

Pro-Glu-Glu-Cys-Gly Pro-Glu-Glu-Cys-Gly
Amino acids

2016 Paul Billiet ODWS

Disaster
Normal gene Substitution mutation
GGTCTCCTCACGCCA GGTCTCCTCACTCCA

CCAGAGGAGUGCGGU CCAGAAGAGUGAGGU
Codons

Pro-Glu-Glu-Cys-Gly Pro-Glu-Glu-STOP
Amino acids

2016 Paul Billiet ODWS

Mutations: Inversion
Inversion mutations, also, only affect a small part of the
gene
Normal gene Inversion mutation
GGTCTCCTCACGCCA GGTCCTCTCACGCCA

CCAGAGGAGUGCGGU CCAGGAGAGUGCGGU
Codons

Pro-Glu-Glu-Cys-Gly Pro-Gly-Glu-Cys-Gly
Amino acids

2016 Paul Billiet ODWS

Mutations: Additions
A frame shift mutation

Normal gene Addition mutation

GGTCTCCTCACGCCA GGTGCTCCTCACGCCA

CCAGAGGAGUGCGGU CCACGAGGAGUGCGGU
Codons

Pro-Glu-Glu-Cys-Gly Pro-Arg-Gly-Val-Arg
Amino acids

2016 Paul Billiet ODWS

Mutations: Deletions
A frame shift mutation

Normal gene Deletion mutation

GGTCTCCTCACGCCA GGTC/CCTCACGCCA

CCAGAGGAGUGCGGU CCAGGGAGUGCGGU
Codons

Pro-Glu-Glu-Cys-Gly Pro-Gly-Ser-Ala-Val
Amino acids

2016 Paul Billiet ODWS

Mutations of hemoglobin
Haemoglobin is a tetramer = 4 polypeptides
2 and 2 -chains
The -chain gene is found on chromosome 11
The -chain gene is found on chromosome 16
The nucleotide sequences have been worked out
Several inherited diseases occur on the -chain,
(146 amino acids).

2016 Paul Billiet ODWS

 haemoglobin sense strand cDNA
sequence
cDNA (complementary DNA) is obtained by
back-transcribing the mRNA used to translate the
polypeptide
So cDNA has no introns
This is done using reverse transcriptase
enzyme.

2016 Paul Billiet ODWS

 Methionine initiator

ATG GTG CAT CTG ACT CCT GAG GAG AAG TCT GCC
GTT ACT GCC CTG TGG GGC AAG GTG AAC GTG GAT
GAA GTT GGT GGT GAG GCC CTG GGC AGG CTG CTG
GTG GTC TAC CCT TGG ACC CAG AGG TTC TTT GAG
TCC TTT GGG GAT CTG TCC ACT CCT GAT GCT GTT
ATG GGC AAC CCT AAG GTG AAG GCT CAT GGC AAG
AAA GTG CTC GGT GCC TTT AGT GAT GGC CTG GCT
CAC CTG GAC AAC CTC AAG GGC ACC TTT GCC ACA
CTG AGT GAG CTG CAC TGT GAC AAG CTG CAC GTG
GAT CCT GAG AAC TTC AGG CTC CTG GGC AAC GTG
CTG GTC TGT GTG CTG GCC CAT CAC TTT GGC AAA
GAA TTC ACC CCA CCA GTG CAG GCT GCC TAT CAG
AAA GTG GTG GCT GGT GTG GCT AAT GCC CTG GCC
CAC AAG TAT CAC TAA
Nonsense terminator
2016 Paul Billiet ODWS
 Mutation Codon Change to DNA Change in
sense strand Amino Acid
S (sickle cell 6 GAG to GTG Glu to Val
anaemia)
C (cooleys 6 GAG to AAG Glu to Lys
syndrome)
GSan Jose 7 GAG to GGG Glu to Gly
E 26 GAG to AAG Glu to Lys
MSaskatoon 63 CAT to TAT His to Tyr
MMilwauki 67 GTG to GAG Val to Glu
OArabia 121 GAA to GTA Glu to Val

2016 Paul Billiet ODWS

 Sickle Cell Anaemia

Sickle cell anemia

www.netwellness.org/.../images/en/1223.jpg

Blood smear (normal)

137.222.110.150/calnet/cellbio/image/blood%20...
Normal haemoglobin
Sickle Cell Haemoglobin
Two HbS molecules
sticking together